In vitro and in vivo cytotoxic activity of anti-human leukemia monoclonal antibodies SN5c and SN6 daunorubicin conjugates.
Murine monoclonal antibodies SN5c specific for the common acute lymphoblastic leukemia antigen (CALLA) and SN6 specific for a novel GP160 tumor associated antigen expressed on non-T ALL and myelomonocytic leukemia cells were conjugated to daunorubicin via an intermediate dextran carrier. The resulting monoclonal antibody-daunorubicin conjugates retained the immunoreactivity of the unlabeled antibody to antigen positive leukemia target cells. In addition, these conjugates demonstrated selective cytotoxic activity when tested against a panel of human leukemia cell lines and/or human leukemia patient samples of peripheral blood or bone marrow origin. The SN5c and SN6-daunorubicin immunoconjugates were superior to a non-specific isotype matched MOPC-daunorubicin conjugate in in vitro cytotoxicity assays. Free daunorubicin, however, was more cytotoxic than either immunoconjugate but lacked selectivity. SN5c-daunorubicin and SN6-daunorubicin combined were as effective as free daunorubicin when used for in vivo therapy and led to complete ablation of established NALM-6 tumors in an athymic nude mouse model. The SN5c-daunorubicin conjugate was also shown to be significantly less toxic than free daunorubicin in non-tumor bearing Balb/c mice. These studies indicate that mAb-daunorubicin conjugates can be constructed which retain specific binding and exhibit selective cytotoxicity against human leukemia cells and suggest that they may have therapeutic applications.